• Rheumatoid arthritis appears three times more often in women
• Women need to know whether they can stop taking drugs while pregnant 
• Genetic markers could predict who will improve and who will worsen during pregnancy 

When women with rheumatoid arthritis (RA) plan to become pregnant, many anguish over whether to stop their medications, risking a flareup in their disease, or continue with medication and risk possible harm to the baby.

About 50% to 75% will see their disease naturally improve during pregnancy for not-yet-known reasons, while others may see a worsening of their RA. But they have had no way of knowing which would happen to them.

Now, Northwestern Medicine scientists have identified, for the first time, genetic markers before pregnancy that could predict who will improve and who will worsen.

The study was published this week in Arthritis Research & Therapy.

RA is an incurable disease that affects 1% of the adult world population and occurs three times more often among women. It leads to significant disability as a result of inflammation of the joints as well as destruction of cartilage and bone. 

“When women with RA go through pregnancy, there often is a natural improvement,” said lead study investigator Damini Jawaheer, research associate professor of medicine in rheumatology at Northwestern University Feinberg School of Medicine. “They describe it as ‘a miracle.’ They say ‘I have never felt this good with any medication I have taken.’ But the cause of this improvement is a complete mystery.

“If women with RA can know in advance whether they are likely to see their disease disappear during pregnancy, they know they can go off their drugs. Some RA drugs are toxic and affect the fetus, while others are considered safe. But some women with RA don’t want to take any drugs during pregnancy, not even the ones considered safe.”

Being able to predict who will improve and who will worsen will help women in their pregnancy planning and will also help to focus treatment during pregnancy only to those women who are predicted to worsen, Jawaheer said. Furthermore, women who are predicted to improve and their fetus will not be unnecessarily exposed to medications. 

Jawaheer and her team found that, before pregnancy, a group of white blood cells called neutrophils were highly expressed among the women who improved during pregnancy, and some genes related to B cells were highly expressed among women who worsened.

This field has not been well studied partly because it is difficult to find women for a pregnancy study before they get pregnant, Jawaheer said.

She and colleagues were able to conduct the study because they’d previously established a unique pregnancy cohort in Denmark, which enrolled women with RA and healthy women before pregnancy and followed them over time to determine who improved and who worsened during pregnancy. Using blood samples collected from those women before pregnancy, they examined the levels of different genes expressed in the blood. Blood samples were collected before pregnancy from 19 women with RA and 13 healthy women enrolled in the prospective pregnancy cohort.

Next, Jawaheer plans to conduct a study in a larger cohort of women to validate these findings. Additionally, her lab is trying to figure out why RA improves during pregnancy. 

“How is nature making an incurable disease go away?” she asked. “If we can understand how pregnancy induces a natural improvement, we can use that as a model to develop a new medication that would be safer and could improve the lives of the women and men living with this terrible disease.”

In a groundbreaking study published in JAMA Pediatrics on October 2, 2023, researchers at Boston Children’s Hospital shed new light on the evolving nature of Autism Spectrum Disorder (ASD) diagnoses in early childhood. Diagnosing ASD at a young age is important for early intervention and treatment, but this new study suggests that not all kids continue to meet the criteria for ASD as they get older.

The team found that 37% of children diagnosed with ASD as toddlers no longer meet the criteria for ASD around the age of six. Children with lower adaptive skills—essential everyday abilities encompassing communication, self-care, and decision-making—tend to be more likely to have ASD persist later in life.

These findings underscore the nuanced nature of ASD and the importance of ongoing assessments throughout a child’s developmental journey. Elizabeth Harstad, MD, MPH, Attending Physician in Developmental Medicine at Boston Children’s and the leader of the study, emphasizes the significance of seeking evaluations for developmental concerns and encourages parents and caregivers to remain open to the possibility of evolving diagnoses over time.

Dr. Harstad notes, “It is important to recognize that diagnoses can evolve as a child develops. Our research shows how important it is that we monitor kids over time, because some children may really have changes in their social communication and behavioral function. This underscores the need for continuous assessments and adaptable intervention strategies.”

While the study provides crucial insights into the developmental trajectory of ASD, William Barbaresi, MD, Chief of Developmental Medicine at Boston Children’s and senior author on the paper, emphasizes the need for further evidence to determine the effectiveness of interventions on long-term outcomes. All of the children in this study received interventions after their initial ASD diagnosis, with the highest amount of interventions received in the 18 months after diagnosis. The team did not find a significant relationship between the persistence of ASD and intensity of interventions received by children in the 18 months after the initial diagnosis. Thus, these findings suggest that more research on the impacts of individualized interventions on development is needed.

The implications of this research are far-reaching, as it calls for a reevaluation of current practices in caring for young children with ASD. The study signals the need for a shift towards a more dynamic and individualized approach to intervention.

“It is possible that children who no longer have autism at age six may have responded better to treatment than children whose autism persisted. The findings of the study should cause a very frank reconsideration of the need for far more research to understand if current treatment for autism is working, or if major new efforts to develop treatment approaches are needed,” said Dr. Barbaresi.

The study focused on individuals with prediabetes who were successful in reducing their body weight by at least 5% through a 12-month lifestyle intervention.

Prediabetes is a condition that precedes type 2 diabetes and increases the risk of heart attack, kidney and eye disease, and several types of cancer. Currently, there is no approved drug therapy for prediabetes available. Scientists at the German Center for Diabetes Research (DZD) now show how and by which mechanisms prediabetes can be brought into remission, i.e. into a state in which blood glucose levels return to normal.  The multicenter study of the DZD also shows that remission of prediabetes protects against type 2 diabetes and is associated with better kidney and vascular function in the long term. Interestingly, the underlying mechanisms are different from those in type 2 diabetes remission, the researchers report in The Lancet Diabetes & Endocrinology.

People with type 2 diabetes have an increased risk of heart attack, kidney disease and stroke, and a higher mortality risk. Type 2 diabetes was thought to be irreversible until a few years ago. We now know that type 2 diabetes can be put into remission in a significant number of individuals through substantial weight loss. However, this remission rarely lasts as most people typically develop type 2 diabetes again within a few years.

“We aimed to explore the feasibility of commencing earlier and implementing preventive measures already at a stage that precedes type 2 diabetes, namely prediabetes, with the aim of reversing it,” elucidates senior author Prof. Dr. Andreas Birkenfeld, Medical Director of Medical Clinic IV at Tübingen University Hospital, and Director of the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen. This could be crucial for patients with prediabetes as they are at increased risk to develop type 2 diabetes as well as heart, kidney, and eye complications among others.

But what causes prediabetes to go into remission? Scientists from the Institute of Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich and the Department of Diabetology, Endocrinology, and Nephrology at the University Hospital of Tübingen, conducted a post-hoc analysis on participants with prediabetes from the Prediabetes Lifestyle Intervention Study (PLIS) to investigate this question.

In this randomized-controlled multicenter study conducted by the DZD, 1,105 individuals with prediabetes underwent a lifestyle intervention involving a healthy diet and increased physical activity for a duration of one year. The researchers then assessed the 298 participants who had achieved a minimum weight loss of five percent as a result of the intervention. Responders were the participants whose fasting blood glucose, 2-hour glucose, and HbA1c levels had normalized within twelve months, indicating that they had gone into remission. Non-responders were individuals who did not achieve remission despite losing weight and still had prediabetes.

Contrary to the researchers’ initial assumptions, it was not weight loss that distinguished those who went into remission from those who did not, as there was no difference in relative weight loss between responders and non-responders. However, individuals who achieved remission demonstrated a notable improvement in insulin sensitivity compared to non-responders. In essence, they were able to enhance their sensitivity to insulin, a hormone that lowers blood glucose levels, significantly more than those who did not respond.  Nonetheless, the quantity of insulin secreted remained unaltered in both groups. This difference is critical compared to type 2 diabetes remission, which depends primarily on enhanced insulin secretion.

Reducing abdominal fat mass may help reverse prediabetes

To determine the cause of increased insulin sensitivity in responders, the researchers conducted a comparative analysis of the two groups. The responders had lost more abdominal fat compared to non-responders despite losing the same amount of body weight. Visceral abdominal fat is located directly in the abdominal cavity and surrounds the intestines. Its impact on insulin sensitivity is partially attributed to an inflammatory response in adipose tissue.

Indeed, participants who went into remission also had fewer inflammatory proteins in their blood. “Since the responders showed a reduction in abdominal fat in particular, it will be important in the future to identify the factors that promote the loss of this fat depot,” says Arvid Sandforth, one of the two lead-authors. Surprisingly, there were no differences between the two groups in the reduction of liver fat, which is also an important risk factor for the development of diabetes.

Participants who achieved remission showed a 73 percent reduced risk of developing type 2 diabetes even two years after the end of the lifestyle intervention. They also showed reduced markers of kidney damage and better status of their blood vessels.

Currently, treatment of prediabetes consists of weight reduction and lifestyle improvement to delay the onset of type 2 diabetes – but without glucose-based targets to guide the treatment process. The DZD’s new analysis fills this gap: “Based on the new data, remission should be the new therapeutic target in people with prediabetes. This has the potential to change treatment practice and minimize the complication rate for our patients,” says co-first author Prof. Dr. Reiner Jumpertz-von Schwartzenberg.

According to the study, remission in prediabetes can be considered to have occurred when fasting blood glucose falls below 100 mg/dl (5.6 mmol/l), 2-hour glucose below 140 mg/dl (7.8 mmol/l), and HbA1c below 5.7 percent. The likelihood of remission increases when body weight is reduced and waist circumference decreases by at least about 4 cm in women and about 7 cm in men. Researchers state that these criteria can now be used as biomarkers.

Patients living with fibromyalgia (FM) – a disease that predominantly affects women and is characterized by chronic pain, fatigue and brain fog – often find limited treatment options and a scarcity of explanations for their symptoms. Research led by Mass General Brigham investigators has found that cognitive behavioural therapy (CBT) can significantly reduce the burden of FM by, in part, reducing pain-catastrophizing, a negative cognitive and emotional response that can intensify pain through feelings of helplessness, rumination and intrusive thoughts. This finding is backed by neuroimaging data, evidencing reduced connectivity between regions of the brain associated with self-awareness, pain and emotional processing. Results are published on September 20 in Arthritis & Rheumatology.

“In this study, we looked at the interplay between psychological processes and the brain’s connectivity patterns in response to pain,” said co-senior author Robert Edwards, PhD, a clinical psychologist in the Department of Anesthesiology, Perioperative & Pain Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “We wanted to explore how CBT, a talk therapy aimed at combatting maladaptive thoughts, can enhance individuals’ daily functioning and alter the brain’s processing of pain-related information.”

Edwards explains that CBT can reduce negative cognitive and emotional responses to pain. He says that while these responses are normal, they can amplify the disabling effects of chronic pain and make conditions like FM more burdensome.

The research team for the study included researchers from three Mass General Brigham members: Spaulding Rehabilitation Hospital, Brigham and Women’s Hospital and Massachusetts General Hospital. Mass General Brigham brings together 16 member institutions, including academic medical centres, top-tier speciality hospitals, community hospitals and more. Research that spans more than one of these entities is more than the sum of its parts, helping to provide insights and unique perspectives from multiple settings and areas of expertise.

Researchers recruited 98 women, randomly assigning 64 to a treatment group receiving CBT and 34 to a control group that received education about FM and chronic pain but was not taught specific CBT techniques. All participants were between 18 and 75 years old and had a confirmed FM diagnosis for at least six months. All participants completed several validated pain and quality of life questionnaires to collect baseline data.

Each group participated in eight intervention sessions, consisting of 60–75-minute visits with a licensed mental health provider. Participants were primarily assessed for their levels of pain interference, or a measure of how much their pain disrupted their daily activities, pain catastrophizing, pain severity and the overall impact FM had on patients’ quality of life.

Results demonstrated that those who underwent CBT experienced significantly greater reductions in pain interference. CBT participants also exhibited significantly less pain catastrophizing and reported that their FM symptoms had significantly less impact on their daily lives.

The team saw evidence that after undergoing CBT, patients experienced changes in the activities of all three networks that suggested a diminished focus on pain.

“Before participants undergoing CBT, we saw that certain parts of the brain linked to self-awareness and sensation were very connected, suggesting patients were pertinently aware of the pain sensation they were experiencing and internalized these symptoms,” said co-first author Jeungchan Lee, PhD, an instructor in the Department of Physical Medicine and Rehabilitation based at Spaulding Rehabilitation Hospital and the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital. “After CBT, these connections were significantly less strong, suggesting that patients were better at separating themselves from their pain after therapy.”

This study was limited to women, partly because of its high prevalence, and partly to eliminate confounding gender differences in brain activity. In the future, the researchers hope to collect data from men and non-binary patients with FM. Additionally, CBT includes several therapeutic components, and these results cannot be generalized to assess the impact across all forms of CBT on reducing FM chronic pain.

Both Lee and Edwards agree that these findings ultimately suggest that complex chronic pain conditions like fibromyalgia should be addressed with various pharmacological and cognitive therapies.

“I hope that these findings motivate healthcare providers to consider CBT as an effective treatment option to reduce the impact of pain patients experience,” explained Edwards. “Chronic pain conditions like fibromyalgia involve long-standing patterns of changes in the central nervous system, and CBT is one among many treatment options, such as medication and physical therapy, that we know can be beneficial for those living with FM.”

Australian patients with chronic health issues prescribed medical cannabis showed significant improvements in overall health-related quality of life and fatigue in the first three months of use, along with improvements in anxiety, depression, and pain. Interestingly, cannabis therapy did not seem to improve reported sleep disturbances, according to a study published September 6, 2023 in the open-access journal PLOS ONE by Margaret-Ann Tait from the University of Sydney, Australia, and colleagues.

Since 2016 in Australia, medical cannabis has been approved for prescription to patients with health conditions unresponsive to other treatment. Tait and colleagues surveyed a group of Australians with chronic health conditions prescribed medical cannabis to better understand any changes in patient-reported outcomes following cannabis treatment in this population.

The authors used survey responses from 2327 Australian patients with chronic health issues prescribed medical cannabis (THC and CBD dissolved in a medium-chain triglyceride (MCT) carrier oil) between November 2020 and December 2021. Patients were surveyed about their self-reported health-related quality of life, pain, sleep, anxiety, and depression prior to beginning cannabis therapy, after two weeks of treatment, then once a month for three months.

63 percent of the surveyed patients were female, with an average age of 51 years (range 18-97 years). The most-reported conditions being treated were chronic pain (69 percent); insomnia (23 percent); anxiety (22 percent); and anxiety/depression (11 percent); half of patients were being treated for more than one condition. Patients reported significant, clinically-meaningful improvements in health-related quality of life and fatigue measurements across the three months surveyed. Patients also reported clinically meaningful reductions in pain and significant improvements for moderate-severe anxiety and depression. However, though many patients were prescribed cannabis for insomnia, there were no overall improvements in patient-reported sleep disturbance.

The authors did not measure adverse effects as part of the study, though 30 patients formally withdrew from the study due to “unwanted side effects”. Regardless, these results suggest medical cannabis may be effective in helping manage previously-untreatable chronic conditions. The authors also note that more research and development of the cannabis oil products used in this study may be needed in order to successfully treat patients with insomnia and sleep disorders.

The authors add: “Within the first three months of medicinal cannabis therapy, participants reported improvements in their health-related quality of life, fatigue, and health conditions associated with anxiety, depression, and pain.”